Preparation of 4-imidazolin-2-ones

ABSTRACT

A class of 4-imidazolin-2-ones are prepared by the cyclization of a urea prepared by the reaction of 2-halo-alken-1-yl amine and an isocyanate. The 4-imidazolin-2-ones are useful as intermediates in the manufacture of plant regulants. Representative of this class is 1-isopropyl-3-(3,4dichlorophenyl)-4-methyl-4-imidazolin-2-one.

United States Patent Dixon et a1. 5] Dec. 2, 1975 [54] PREPARATION OF 4-IMIDAZOLIN-2-ONES 3,355,457 11/1967 Wright, Jr. et a1 260/309.6 Inventors: William D. Dixon Kirkwood; Bracey 3,723,455 3/1973 Chupp 260/309.6

R. Dangerfield, St. Louis, both of O ER PUBLICATIONS Theilheimer, Synthetic Methods of Organic Chemis- [73] Assignee: Monsanto Company, St. Louis, Mo. Karger New York 1964' Theilheimer, Synthetic Methods of Organic Chemis- [221 Flledl 19, 1974 try, p. 206, s. Karger, N.Y., 1964. [21] Appl. No.: 525,257

Primary Examiner-Ethel G. Love Related Apphcatlon Data Attorney, Agent, or Firm-Richard H. Shear [62] Division of Ser. No. 376,494, July 5, 1973,

abandoned. ABSTRACT [52] 5 CL 260/3095; 260/553 260/583 G; A class of 4-imidazo1in-2-ones are prepared by the cy- 424/273 clization of a urea prepared by the reaction of 2-halo- 51 1111. 1:1. c071) 49/34 alken-l-yl amine and isocyanate- The 4-imidalolin- [58] Field of Search 260/309.6 l-ones are useful as intermediates in the manufacture of plant regulants. Representative of this class is l- 5 Ref Cited isopropyl-3-(3,4-dichlorophenyl)-4-methyl-4- UNITED STATES PATENTS 3,136,776 6/1964 Stoffel 260/309.6 5 Claims, N0 Drawings wherein R is lower alkyl, R is lower alkyl or, and preferably, hydrogen, R is lower alkyl or hydrogen, Z is fluoro, chloro, bromo lower alkyl, halo lower alkyl or lower alkoxy and n is an integer zero through 2.

The N-(2-halo-alken-lyl-) urea provided by this invention as precursors for the above described 4- imidazolin-2-ones can be represented by the following fonnula wherein X is halo, preferably chloro or bromo and R, R R, Z and n are as defined above in formula (1).

The N-(2-halo-2-alken-l-yl) ureas can be prepared by reacting on appropriate (2-halo-2-alken-l-yl) amine with an appropriate isocyanate set forth schematically as follows where R, R R", X, Z and n are as previously defined.

As employed herein, the term lower designates those aliphatic radicals of notmore than 4 carbon atoms in straight or branched chain. Representative lower alkyl substituents are methyl, ethyl, propyl, isopropyl, butyl, tert. butyl and the like. Where the substituent is alkoxy, it can be methoxy, ethoxy, propoxy,

2 isopropoxy, butoxy, sec. butoxy and the like. When n is 2 the substituents represented by Z can be like or unlike.

The reaction of the appropriate amine and the isocyanate is well understood by those skilled in the art. In general the reaction is conducted in the presence of an inert solvent, for example ethers, such as, diethyl ether, di-isoproyl ether, methylbutyl ether tetrahydrofuran, the alkanes, such as n-hexane, n-heptane, cyclohexane, the esters, such as, ethyl acetate, propyl acetate, and other solvents. The ethers are generally preferred for convenience. The temperature of the reaction is not critical and will depend upon the particular reactants and in general will be between room temperature and the reflux temperature of the system. The ratio of the reactants can vary using either a slight excess of the amine or the isocyanate. Usually the reactants are used in a ratio of 1:1. Recovery of the desired urea can be obtained by various means such as filtration, washing, evaporation of the solvent and the like. Purification of the urea often is not required in order to produce the 4-imidazolin-2-ones in accordance with the instant invention.

The required 2-halo-2-alken-l-yl amines and appropriate isocyanates are readily prepared by methods known in the art. For example, US. Pat. No. 2,278,527 to F. F. Rust and W. E. Vaughan describe a vapor phase process of halogenating via substitution of halosubstituted unsaturated hydrocarbons using oxygen to catalyze the reaction. Such halogenated halo-substituted olefins can be reacted with a primary amine to form the appropriate 2-halo-2-alken-l-yl amine as shown schematically as follows where R, R R and X are as previously defined.

The above secondary amine is reacted with an aryl isocyanate using well known procedures to prepare the novel ureas as shown schematically where R, R R X, Z and n are as previously defined.

The above novel ureas are required as intermediates in the method of making 4-imidazolin-2-ones in accordance with this invention. Thus, another embodiment 3 4 of this invention isthe method of preparing 4-imidazo- The invention is further illustrated by the following l1n-2-ones by cyclizing a solution of the appropriate examples. All parts and percentages are by weight and urea in the presence of base. This reaction is set forth temperature is in degrees Centigrade unless otherwise schematically as follows specified.

R 0 H base 0 R -CH=C- CH-N-C-N- R -NCN- I 1 n X R C C Zn Zn R2 CH2 where R, R R X, Z and n are as previously defined. EXAMPLE 1 In conducting the cyclizing reaction the temperature of the system can vary over a wide range, for example, Preparatlon of p py z'chloroallyl amme from room temperature or below up to the reflex tem- To a stirred Solution of 297 g 5 mol) of isopropyla perature of the System Generally good result-S are mine and 127 ml of water in a suitable vessel is added tained at elevated temperatures in the range of about 40 to about 90 C or more dependent upon the solvent employed. Conducting the cyclization at a temperature from about 60 to about 80 C is usually very satisfacdropruise over a 2 hour period about 133g (1.19 mol) of 2.3-dichloro-1-propene. After the addition the reaction is heated at about 70 for 4 hours, cooled and about 66.6g (1.7 mol) sodium hydroxide is added.

tory.

This cyclization reaction can be conducted at pres- 5 After stirring about minutues, the top layer is sepasures ranging from subatmospheric to superatmosrated, filtered and dried with solid sodium hydroxide pheric pressure. Usually, the reaction is conducted at until no more water separated The liquid, 145 is normal atmospheric pressure for convience which prodistilled and after a forerun at 310/760 mm Hg the vides ood ields. Suitable solvents which can be used in carying out this cyclization are, for example, di- 30 i collecteg as methyl sulfoxide, dimethylformamide, tetrahydrofuran, 13571 H m "sopropy methanol, ethanol, and the like. Selection of an approchloroanylamme 129-45 (81% yleld) priate solvent is not critical. Particularly good results are obtained with ethanol which is preferred. Suitable bases useful in the process of preparing the 4-imidazolin-Z-ones are, for example, the hydroxides such as potassium hydroxide, sodium hydroxide, the alkoxides, Such Potassium t'butoxide and other equivalent To a stirred solution of 11.9g (0.1 mol) of phenyl isobases can be used Usually. an.excess of the base 15 used cyanate and 200 ml of ether in a suitable vessel is added to assure complete cyclization of the N-(2-ha1o-2- 40 dropwise g 01 of p py chloroal g g porfcomgence and economy poms lyl amine in 50 ml of ether. The reaction is stirred for slum y fox] 6 is pre erre about 15 hours and the solvent is removed in vacuuo.

The 4-imidazolin-2-ones, prepared by the process of the instant invention, have been previously described in p sclratchmg a solld 1S Obtamedy tall ati n U.S. Pat. No. 3,136,776 to P. J. Stoffel. The preparaof the product from carbon tetrachloride pet. ether tion of the 4-imidazolin-2-ones described in U.S. Pat. gives 21.3g (84.7%) of 1-(2-chloroallyl)-l-isopropyl-3- No. 3,136,776 utilizes an alkynyl urea treated with phenyl urea having a melting point f 7 9'. peltachmide Prepare a 'E. Anal. Calcd. for C H N 0 01: C,6l.77; H. 6.78; methyl-imidazolium chloride precursor w 1c 18 50 1108'F0undzC, 61.83; .0

treated with a base in an aqueous system to provide the I 4-methyl-imidazolin-2-ones. The preparation of the Using the procedure of Example II, but replacing the imidazolin2-ones in accordance with U.S. Pat. No. phenyl isocyanate with an appropriate substituted 3,136,776 is limited by the required use of alkynl defiv' phenyl isocyanate the following ureas are prepared and atives, which are highly unstable and the explosive set forth as examples properties of the alkynl precursors are unsatisfactory in EXAMPLE II Preparation of 1-(2-ch1oroallyl)-l-isopropyl-3-phenyl urea the commercial preparation of the 4-imidazolin-2-ones. [I] 1-(2-chl0r0ally])-1-isopropy1-3-O chlorophenyl The instant process avoids the use of any alkynl deriyaurea mp 4 44 tives and provides an economical method of preparing IV 1 11 1)- 1-i p pyl-3-p-t0ly1 urea mp.

the 4-imidazolin-2-ones in good yield without the requirement of employing costly safeguards required by V y p py a p the use of alkynyl derivatives. nyl) urea mp 0 In addition to the bacter ostatic activity of the 4- VI 1 yn p py (p w wh imidazolin-Z-ones disclosed in U.S. Pat. No. 3,136,776 urea p 912940 the 4-imidazolin-2-ones are useful as intermediates to produce 2-imino derivatives of substituted imidazoles which are effective plant growth regulants as more fully described in pending patent application of G. L. Eilrich and W. D. Dixon, Ser. No. 329,787 filed Feb. 5, 1973.

In like manner employing the procedure of Example 11 but replacing the N-isopropyl-N-2-chloroallyl amine with N-alkyl-N-halo-2-a1ken-l-yl amines provides the desired 1-a1kyl-1-(2-halo-2-alken-l-yl) -3-aryl ureas.

EXAMPLE VII Preparation of l-isopropyl-3-(3 ,4-dichlorophenyl)-4-methyI-4- imidazolin-2-one To a stirred suspension of finely powdered potassium hydroxide, 12g in 35ml of dimethyl sulfoxide at 65 is added, dropwise over a period of about 30 minutes, a solution of 53.4g (0.16 mol) of l-(2-chloroallyl)-1-isopropyl-3-(3,4-dichorophenyl urea in 75ml of dimethyl sulfoxide. The reaction is heated hours at about 70 and cooled and poured over ice. A solid product is obtained which is removed by filtration and air dried, 45.1g (99% yield). Recrystallization of the product from ethyl acetate pet. ether provides 403g (89% yield) of l-isopropyl-3-(3,4-dichlorophenyl)-4-methyl- 4-imidazolin-2-one having a melting point of 1 10-1 1 1 C. The following structure is confirmed by IR and NMR spectral anaylsis.

CI-I O ;T t c1 CH c C III CH Anal. Calcd. for c,,i-i,,N,o C1,.- c, 54.75; H. 4.95; N, 9.82. Found: C, 55.14; H, 5.20; N, 9.88.

Following the procedure of Example VII but replacing the urea with other appropriate ureas the following compounds are prepared.

VIII 1-isopropyl-3-phenyl-4-methyl-4imidazolin- 2-one IX 1-isopropyl-3 -p-ethoxyphenyl-4-methyl-4- filed concurrently herewith, Ser. No. 376,493 filing date July 5, 1973, now U.S. Pat. No. 3,887,577.

Although this invention has been described with respect to specific modifications, the details thereof are not to be construed as limitations, for it will be apparent that various equivalents, changes and modifications may be resorted to without departing from the spirit and scope thereof and it is understood that such equivalent embodiments are intended to be included herein.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

l. A process for preparing a compound of the formula wherein R is lower alkyl, R is lower alkyl or hydrogen, R is lower alkyl or hydrogen, Z is independently fluoro, chloro, bromo, lower alkyl, halo lower alkyl or lower alkoxy and n is an integer zero through 2 which comprises cyclizing a solution of a compound of the formula wherein R R R, Z and n are the same as hereinabove defined and X is halo in the presence of a base at a temperature in the range of about 20C. to the reflux temperature of the system.

2. The process of claim 1 wherein the urea is in solution with dimethyl sulfoxide.

3. The process of claim 1 wherein the urea is in solution with ethyl alcohol.

4. The process of claim 1 wherein the base is potassium hydroxide.

5. The process of claim 1 wherein a solution of I-(2- chloroallyl)-l-isopropyl-3-(3,4-dichlorophenyl) urea in ethyl alcohol is cyclized with potassium hydroxide at a temperature of about 65 C. 

1. A PROCESS FOR PREPARING A COMPOUND OF THE FORMULA
 2. The process of claim 1 wherein the urea is in solution with dimethyL sulfoxide.
 3. The process of claim 1 wherein the urea is in solution with ethyl alcohol.
 4. The process of claim 1 wherein the base is potassium hydroxide.
 5. The process of claim 1 wherein a solution of 1-(2-chloroallyl)-1-isopropyl-3-(3,4-dichlorophenyl) urea in ethyl alcohol is cyclized with potassium hydroxide at a temperature of about 65* C. 